Rotaviruses are the single most important etiologic agents of severe diarrhea in infants and young children in both developed and developing countries. It was estimated by the IOM that in the developing countries, annually, over eight million infants and young children develop severe rotavirus diarrhea, and over 870,000 die. Thus, there is an urgent need for a rotavirus vaccine that can prevent severe rotavirus diarrhea during the first two years of life when the disease is most serious. This is a major goal of Section. The "Jennerian" approach to vaccination, which involves the use of a live vaccine virus strain derived from a non-human host, has been evaluated in clinical trials using surrogate rotavirus strains of bovine origin (by others) or of simian rhesus monkey origin by us. This approach has had limited success because serotype-specific immunity against each of the four medically important human rotavirus VP7 serotypes could not be achieved consistently in infants less than six months of age with such a monovalent vaccine. We are currently pursuing a modified "Jennerian" approach in which a quadrivalent rotavirus vaccine containing (i) rhesus rotavirus (RRV) (VP7 serotype 3) and (ii) three human rotavirus-RRV reassortants, each possessing 10 RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity, is given orally at two months of age. Placebo-controlled field trials with individual reassortant vaccines or the quadrivalent vaccine have been completed or are in progress. The vaccines appear to be quite promising, in general. A significant reduction in the incidence of rotavirus diarrhea in vaccines when compared to placebo recipients has been observed in most, but not all, of the studies.